Triazole Units Research Articles

Comprehensive Review on the Synthesis of [1,2,3]Triazolo[1,5-a]Quinolines.

This report outlines the evolution and recent progress about the different protocols to synthesize the N-heterocycles fused hybrids, specifically [1,2,3]triazolo[1,5-a]quinoline. This review encompasses a broad range of approaches, describing several reactions for obtaining this since, such as dehydrogenative cyclization, oxidative N-N coupling, Dieckmann condensation, intramolecular Heck, (3+2)-cycloaddition, Ullman-type coupling and direct intramolecular arylation reactions. We divided this review in three section based in the starting materials to synthesize the target [1,2,3]triazolo[1,5-a]quinolines. Starting materials containing quinoline or triazole units previously formed, as well as starting materials which both quinoline and triazole units are formed in situ. Different methods of obtaining are described, such as metal-free or catalyzed conditions, azide-free, using conventional heating or alternative energy sources, such as electrochemical and photochemical methods. Mechanistic insights underlying the reported reactions were also described in this comprehensive review.

Nucleoside Scaffolds and Carborane Clusters for Boron Neutron Capture Therapy: Developments and Future Perspective.

Nucleosides containing carboranes are one of the most important boron delivery agents for boron neutron capture therapy, BNCT, which are good substrates of hTK1. The development of several nucleosides containing carboranes at early stages led to the discovery of the first generation of 3CTAs by incorporating a hydrocarbon spacer between the thymidine scaffold and carborane cluster and attaching dihydroxylpropyl group on the second carbon (C2) atom of the carborane cluster (e.g., N5 and N5-2OH). Phosphorylation rate, tumor cellular uptake, and retention have been evaluated in parallel to change the length of the tether arm of spacers in these compounds. Many attempts were reported and discussed to overcome the disadvantage of the first generation of 3CTAs by a) incorporating modified spacers between thymidine and carborane clusters, such as ethyleneoxide, polyhydroxyl, triazole, and tetrazole units, b) attaching hydrophilic groups at C2 of the carborane cluster, c) transforming lipophilic closo-carboranes to hydrophilic nidocarborane. The previous modifications represented the second generation of 3CTAs to improve the hydrogen bond formation with the hTK1 active site. Moreover, amino acid prodrugs were developed to enhance biological and physicochemical properties. The structure-activity relationship (SAR) of carboranyl thymidine analogues led to the roadmap for the development of the 3rd generation of the 3CTAs for BNCT.

Synthesis and spectroscopic studies of triazole-based macroheterocycles containing eudesmane-type sesquiterpenoid moieties

Chiral recognition is one of the most important and fascinating areas in supramolecular chemistry. Chiral macrocycles, especially chiral macrocyclic hosts, having stable structures, adjustable internal cavities to encapsulate and complexation have been developed during the last decade. Attention has been paid on the synthesis of covalently linked of rigid units on the side chain of macrocycles with active binding motifs. In this study, new synthetic protocols has been developed for preparation of optically active triazole-based macrocyclic compounds in which eudesmane-type sesquiterpene lactones act as pendent moieties by the implementation of the copper(I)-catalyzed azid-alkyne cycloaddition strategies. The described protocols provided mild reaction conditions, high yields and high atom- and step-economy. New macrocycles with hanging dihydroisoalantolactone units, different combinations of heteroatoms, and ring sizes in the range of 16–36 atoms were characterized by NMR and UV–vis spectroscopy and mass spectrometry analysis. The molecular structures and intermolecular interactions of two new macrocyclic compounds were elucidated using single-crystal X-ray crystallography. Upon addition of Mg(II) or Zn(II) cations to these novel ligands, using titration experiments we observed the formation of 1:1 (16:Mg2+) complexes and 1:1 to 2:1 (16:Zn2+) complexes, respectively, according to stoichiometry. The result suggests that dihydriisoalantolactone and triazole units within the molecules formed complexes with Mg (II) and Zn (II) ions in solution.

Click approach for the synthesis of 1,4-disubstituted-1,2, 3-triazoles of porphyrin-isatin/sulfa drug conjugates based on m-THPP

New porphyrin-isatin/sulfa drugs conjugates based on symmetrical 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin ([Formula: see text]-THPP) with 1,4-regioisomers of 1,2,3-triazole linker were successfully synthesized. The constructed porphyrin-conjugates 15-19 and 22-24 contained mono-, tri- (unsymmetrical), or tetrafunctionalized units of isatin, sulfanilamide and sulfapyridine with 1,2,3-triazole linker. The synthesis of these conjugates was achieved by nucleophilic functionalization of [Formula: see text]-THPP by propargyl bromide followed by zinc metalation to achieve the mono-/tri-/tetrafunctionalized propargyl[Formula: see text]-THPP zinc-complex derivatives 3-5 (alkyne partners). The formed alkyne partners underwent cycloaddition reaction with isatin azide 8, azidosulfanilamide 13 and azidosulfapyridine 14 (azide partners) using click conditions via applying copper (I) catalyzed azide-alkyne cycloaddition (CuAAC). The utilized protocol succeeded in generating amphiphilic conjugates based on [Formula: see text]-THPP in an easy, simple, and quick manner, with high regioselectivity and high yields for potential medicinal and biological applications. The Zn-porphyrin derivatives’ photonic properties were investigated via photoabsorption and fluorescence. The optical properties were also studied and it is obvious that the Zn-porphyrin complex derivatives are different from those of the free-base porphyrin and could be relied on the number of triazole units and bioconjugate type.

Copper-Free Synthesis of Cationic Glycidyl Triazolyl Polymers.

Copper-free synthesis of cationic glycidyl triazolyl polymers (GTPs) is achieved through a thermal azide-alkyne cycloaddition reaction between glycidyl azide polymer and propiolic acid, followed by decarboxylation and quaternization of the triazole unit. For synthesizing nonfunctionalized GTP (GTP-H), a microwave-assisted method enhances the decarboxylation reaction of carboxy-functionalized GTP (GTP-COOH). Three variants of cationic GTPs with different N-substituents [N-ethyl, N-butyl, and N-tri(ethylene glycol) monomethyl ether (EG3)] are synthesized. The molecular weight of GTP-H is determined via size exclusion chromatography. Thermal properties of all GTPs are characterized using differential scanning calorimetry and thermogravimetric analysis. The ionic conductivities of these cationic GTPs are assessed by impedance measurements. The conducting ion concentration and mobility are calculated based on the electrode polarization model. Among three cationic GTPs, the GTP with the N-EG3 substituent exhibits the highest ionic conductivity, reaching 6.8 × 10-6 S cm-1 at 25°C under dry conditions. When compared to previously reported reference polymers, the reduction of steric crowding around the triazolium unit is considered to be a key factor in enhancing ionic conductivity.

Total Synthesis of an Epothilone Analogue Based on the Amide-Triazole Bioisosterism.

Epothilones are 16-membered macrolides that act as microtubule-targeting agents to tackle cancer. Many synthetic analogues have been investigated for their activity, yet often based on macrolide structures. A notable exception is Ixabepilone, an azalide whose metabolic stability and pharmacokinetics are significantly improved. Exploiting the amide-triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit. Together with the synthesis of this new analogue, computational and biological evaluations have been performed too.

The fabrication of a hybrid fluorescent nanosensing system and its practical applications via film kits for the selective determination of mercury ions

Heavy metal ions especially mercury exposure have severe toxic effects on living organisms and human health. Therefore, easy, accessible, and accurate determination strategies for the selective specification of mercury ions are essential for numerous disciplines. In the presented paper, new hybrid fluorescent iron oxide nanoparticles labeled with carbazole and triazole units (CT-IONP) were prepared via surface modification for the spectrofluorimetric determination of Hg2+ in environmental samples. The structure of the new sensing system is characterized via various spectroscopic, thermal, and microscopic techniques. Under optimized conditions, the hybrid system is not only used in fully water media but also highly fluorescent which led to the “turn-off” response towards Hg2+ ion in the presence of various competitive species. The presented sensing system was successfully used for the determination of Hg2+ ions in the wide linear working range (0.02–10.00 µmol.L−1) at nanomolar levels, where the limit of detection and quantification were calculated as 7.38 and 22.14 nmol.L−1. Importantly, the practical application of hybrid material was applied by CT-IONP embedded polycaprolactone (PCL) polymer film kits. The bluish color of fabricated film kits was instantly and dramatically turned colorless-dark patterns after the addition of Hg2+ ions, which resulted in convenient and rapid film test kits for selective detection.

Statement of Retraction: Synthesis of Nanocrystalline Polycalix[4]amides Containing Mesogenic Triazole Units and Investigations of Their Thermo Physical Properties and Heavy Metal Sorption Behavior

Statement of Retraction: Synthesis of Nanocrystalline Polycalix[4]amides Containing Mesogenic Triazole Units and Investigations of Their Thermo Physical Properties and Heavy Metal Sorption Behavior

Novel near-infrared BODIPY-cyclodextrin complexes for photodynamic therapy

To meet the requirements of diagnosis and treatment, photodynamic therapy (PDT) is a promising cancer treatment with less side-effect. A series of novel BODIPY complexes (BODIPY-CDs) served as PDT agents were first reported to enhance the biocompatibility and water solubility of BODIPY matrix through the click reaction of alkynyl-containing BODIPY and azide-modified cyclodextrin (CD). BODIPY-CDs possessed superior water solubility due to the introduction of CD and their fluorescence emission apparently redshifted (>90 nm) on account of triazole units as the linkers compared to alkynyl-containing BODIPY. Moreover, all the BODIPY-CDs were no cytotoxicity toward NIH 3T3 in different drug concentrations from 12.5 to 200 μg/mL, and had a certain inhibitory effect on tumor HeLa cells. Particularly, BODIPY-β-CD exhibited high reactive oxygen species generation and excellent photodynamic therapy activity against HeLa cells compared to other complexes. The cell viability of BODIPY-β-CD was dramatically reduced up to 20% in the concentration of 100 μg/mL upon 808 nm laser irradiation. This architecture might provide a new opportunity to develop valuable photodynamic therapy agents for tumor cells.

Hyperbranched polyimide with triazole core structure for nonvolatile resistive switching memory

AbstractHyperbranched polyimides (HBPIs) possess a unique branched structure, which can make the lowest unoccupied molecular orbitals (LUMOs) degenerate and reduce the bandgap between the highest occupied molecular orbital (HOMO) and LUMO energy levels. The triazole group can facilitate the charge transfer process. Thus, a novel hyperbranched polyimide (HBPI‐TZA‐6FDA) has been prepared from new triazole derivative triamine monomer (TZA) and 4,4′‐(hexafluoroisopropylidene)diphthalic anhydride (6FDA) for memory device. The memory device with the structure ITO/HBPI‐TZA‐6FDA/Al exhibits a low‐threshold voltage of −2.2 V and a high ON/OFF current ratio of about 105. Meanwhile, the memory device shows nonvolatile write once read many times (WORM) type memory behavior and excellent stability with an operation time of 104 at a continuous applied voltage of −1 V. Optical, electrochemical experiments, and molecular simulation have been carried out to illustrate the memory performance. The memory performance is governed by the charge transfer between TZA and 6FDA units. The branched structure and triazole unit can reduce the band gap between HOMO and LUMO energy levels effectively, which is favorable for improving charge transfer and reducing threshold voltage. The HBPI‐TZA‐6FDA‐based memory device is favorable for memory device applications due to its relatively low‐power consumption and high‐operation stability.

Synthesis of substituted triazole-pyrazole hybrids using triazenylpyrazole precursors.

A synthesis route to access triazole-pyrazole hybrids via triazenylpyrazoles was developed. Contrary to existing methods, this route allows the facile N-functionalization of the pyrazole before the attachment of the triazole unit via a copper-catalyzed azide-alkyne cycloaddition. The developed methodology was used to synthesize a library of over fifty new multi-substituted pyrazole-triazole hybrids. We also demonstrate a one-pot strategy that renders the isolation of potentially hazardous azides obsolete. In addition, the compatibility of the method with solid-phase synthesis is shown exemplarily.

Breaking Radial Dipole Symmetry in Planar Macrocycles Modulates Edge-to-Edge Packing and Disrupts Cofacial Stacking.

Dipolar interactions are ever-present in supramolecular architectures, though their impact is typically revealed by making dipoles stronger. While it is also possible to assess the role of dipoles by altering their orientations by using synthetic design, doing so without altering the molecular shape is not straightforward. We have now done this by flipping one triazole unit in a rigid macrocycle, tricarb. The macrocycle is composed of three carbazoles (2 Debye) and three triazoles (5 Debye) defining an array of dipoles aligned radially but organized alternately in and out. These dipoles are believed to dictate edge-to-edge tiling and face-to-face stacking. We modified our synthesis to prepare isosteric macrocycles with the orientation of one triazole dipole rotated 40°. The new dipole orientation guides edge-to-edge contacts to reorder the stability of two surface-bound 2D polymorphs. The impact on dipole-enhanced π stacking, however, was unexpected. Our stacking model identified an unchanged set of short-range (3.4 Å) anti-parallel dipole contacts. Despite this situation, the reduction in self-association was attributed to long-range (~6.4 Å) dipolar repulsions between π-stacked macrocycles. This work highlights our ability to control the build-up and symmetry of macrocyclic skeletons by synthetic design, and the work needed to further our understanding of how dipoles control self-assembly.

Azo-Bridged Triazole Macrocycles: Computational Design, Energy Content, Performance, and Stability Assessment.

Oxadiazole and triazole are extensively investigated heterocyclic scaffolds in the development of energetic materials. New energetic molecules were designed by replacing 1,2,5-oxadiazole with 2H-1,2,3-triazole in the reported conjugated macrocyclic systems to assess the influence on the energetic properties and stability. In addition, nitro groups were introduced in triazole units (N-functionalization) to improve the energetic performance. Energetic properties, including heat of formation, oxygen balance, density, detonation pressure and velocity, and impact sensitivity, were estimated for these triazole-based macrocycles. The replacement of 1,2,5-oxadiazole with 2H-1,2,3-triazole and 2-nitro-1,2,3-triazole significantly enhances the energy content, detonation performance, and noncovalent interactions. The theoretically computed energetic properties of triazole-based macrocycles reveal high positive heats of formation (1507-2761 kJ/mol), oxygen balance (-88.8 to -22.8%), high densities (1.87-1.90 g/cm3), superior detonation velocities (8.41-9.52 km/s), pressures (26.64-40.55 GPa), acceptable impact sensitivity (27-40 cm), and safety factor (51-290). The overall energetic assessment highlights triazole-based macrocycles as a potential framework that will be useful for developing advanced energetic materials.

Chiroptical Recognition of Carboxylates with Charge-Neutral Double-Stranded Zinc(II) Helicates.

Chirality analysis of small molecules for the determination of their enantiopurity is nowadays ruled by streamlined chromatographic methods which utilize chiral stationary phases. Chiroptical probes which rely on host-guest interactions are so far overshadowed by the latter but have the benefit of depending only on common spectroscopic techniques such as CD spectroscopy to distinguish enantiomers and to quantify their ratio. Interest into this receptor-based approach is constantly rising because non-invasive high-throughput screenings with a minimal waste production can be performed. In this study we investigate the possibility to utilize metal-based containers in form of charge-neutral helicates able to recognize anions for this purpose. Key building block of the helicates are triazole units which show rotational freedom and give rise to either a meso-structure or a racemic mixture of the right- and left-handed complex. A chiroptical response of the probe is observed upon recognition of chiral mono- or dicarboxylates and chirality analysis of tartrate is conducted by CD spectroscopy.

Benzotriazole‐Based D–π–A‐Type Photovoltaic Polymers Break Through 17% Efficiency

AbstractBenzo[d][1,2,3]triazole (BTA) unit is one of the most classic electron‐accepting units (A) to construct donor (D)‐π‐A‐type photovoltaic polymers. However, the highest power conversion efficiency (PCE) of organic photovoltaics (OPVs) based on BTA‐containing polymers is restricted to 15–16%, lagging other promising polymers. Thus, investigating the structure‐performance relationship and breaking the efficiency bottleneck of BTA‐based polymers is challenging but critical. Herein, the effects of fusing two thiophene rings at D (PE52), π (PE4), and A (PE39) units of a classic D–π–A‐type BTA‐containing polymer J52‐Cl, respectively, on the backbone conformation, crystallinity, molecular stacking, and photovoltaic performance are systematically investigated. When blended with a BTA‐containing non‐fullerene acceptor (NFA), Y18, all three polymers with extending conjugated backbones can decrease the energy loss of photovoltaic devices. Notably, PE4, with a linear backbone conformation, realizes the champion PCE of 17.08%, with a short‐circuit current density (JSC) of 26.83 mA cm−2, a large breakthrough for BTA‐based photovoltaic polymers. What's more, the photovoltaic device based on PE4:Y18 combination fabricated by a non‐halogenated solvent of o‐xylene also displays an excellent PCE of 16.87%. The results indicate that fusing thiophene rings to BTA‐polymers, especially at π‐bridge, is a simple and effective method to improve the photovoltaic performance via modulating the molecular conformation and crystallinity.

Synthesis, X-ray crystallography, antimicrobial, molecular docking, and DFT study of bis-triazoles linked ampyrone

A new class of bis-triazoles linked with ampyrone molecules was synthesized from ampyrone-linked bis-alkyne with different benzyl azides under Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. All compounds were characterized by FTIR, 1H NMR, 13C NMR, and ESI-MS data. However, the structures of solid crystalline compounds 4a and 4h were finally supported by X-ray crystallographic data. In vitro, antimicrobial activity results of synthesized alkyne 2 and bis-1,2,3-triazoles 4a-4k showed that the incorporation of triazole units has augmented the antimicrobial activity of all compounds, except 4a for E. coli. Also, compound 4f was found potent against all bacterial strains (E. coli, S. aureus, and P. aeruginosa, each with MIC: 0.0178 µmol/mL) with superior efficacy to B. subtilis (MIC: 0.0089 µmol/mL) compared to standard antibacterial drug ciprofloxacin (MIC: 0.0094 µmol/m). Almost all synthesized triazoles showed superior potency to both fungal strains except 4a, 4g, and 4k against R. oryaze, C. albicans, and R. oryaze, respectively. Computational molecular docking and DFT results supported experimental antimicrobial results for improvement in the activity of all triazoles except 4a.

Integrating local polarization in hydrogen bonded organic frameworks for efficient photocatalytic nitrogen fixation

Elaborately designing stabilized hydrogen-bonded organic frameworks (HOFs) with higher charge transfer rate and abundant active sites for efficient photocatalytic nitrogen fixation are urgent and challenging. Herein, a micromolecular hydrogen-based triazole unit integrated into rigid perylene diimide based hydrogen-bonded organic framework (NPDI) has been elaborately designed. Experimental and theoretical results demonstrate that the flexibility and polar micromolecular group embedded in rigid framework not only stabilized HOFs frameworks, but also enhanced the local polarization, electron delocalization and the built-in electric field of HOFs, which greatly promotes exciton dissociation and the carrier transfer. Fortunately, NPDI has excellent photocatalytic nitrogen fixation rate (179 µmol h−1 g−1) and near-infrared NH4+ yield in pure water under ambient conditions. Our work offers deep insights into molecular level regulation for rationally designing efficient HOFs.

Customized hourglass-shaped channels in a copper(II)-organic framework for one-step ethylene purification from ethylene/ethane/acetylene ternary mixtures with high adsorption capacity

One-step purification of C2H4 from C2H2/C2H4/C2H6 ternary mixtures represents an important yet challenging task in chemical industry. Favored adsorption of C2H2 and C2H6 over C2H4 has stringent requirements on pore size and surface chemistry of the adsorbents. We report a Cu-MOF (Cu–L), [Cu0.5(L)0.5]·2DMF (H2L = 4′-(1H-1,2,4-triazol-1-yl)-[1,1ꞌ-biphenyl]-3,5-dicarboxyl)) with one-dimensional hourglass-shaped channels decorated by phenyl rings and triazole units. Suitable pore structure and customized pore surface have endowed Cu–L with high adsorption capacities toward C2 hydrocarbons, and preferential adsorption of C2H2 and C2H6 over C2H4. Separation capability of Cu–L has been confirmed by multicomponent breakthrough experiments and polymer-grade C2H4 can be directly obtained from C2H2/C2H6/C2H4 (1/1/1 and 1/9/90, v/v/v) mixtures. The underlying mechanism of preferential adsorption was revealed by Grand Canonical Monte Carlo simulations and DFT calculations.

Click-Chemistry-Assisted Alteration of Glycosaminoglycans for Biological Applications

AbstractThis short review describes the assistance of click chemistry in the chemical modification of glycosaminoglycans. Through an alkyne-azide 1,3-dipolar cycloaddition reaction, the chemically and physiologically stable triazole unit connects glycosaminoglycans with other labelled or attached functionalities. The synthesized glycosaminoglycan (GAG) conjugates act as drug carriers, forming hydrogels or nanohydrogels for localized drug delivery or injectable GAGs and so on. These are used in research on antithrombotic agents, protein binding, and hepatocyte growth factors, as well as in mechanistic studies of glycosaminoglycans biosynthesis and wound healing.1 Introduction2 Synthetic Modification of GAGS3 Click Chemistry4 Modification of GAGS Applying Click Chemistry5 Conclusions6 Abbreviations

An Effective Additive for Introducing the Triazole Unit of Ensitrelvir: Combination of LiCl and Et3N to Easily Generate Lithium Triazinolate

AbstractAn efficient and robust method was developed to introduce the triazole unit of Ensitrelvir, a COVID-19 therapeutic agent. One of the key steps is introducing the triazole unit in the triazinone with Cs2CO3 and KI in a heterogeneous system. Detailed reaction screening revealed that addition of LiCl allowed the reaction to proceed quantitatively in the presence of inexpensive Et3N, and the selectivity of the N-alkylation was greatly improved. The key to promoting the reaction is the mild formation of the lithium triazinolate accompanied by precipitation of Et3N·HCl (the only insoluble matter in this reaction). Dissolving all the substrates and reagents should contribute to further improvement of the process robustness.